07.02.2019 Working breakfast, European Parliament

LifeTime will present its vision for a healthier Europe at a workshop jointly organized with the Panel for the Future of Science and Technology (STOA) in Brussels. The current status of artificial intelligence applied to early diagnosis and targeted disease intervention will be discussed among researchers and decision-makers.

15.01.2019 – LifeTime Press Release

Europe looks to cells for a healthier future

Our body’s cells are constantly changing. But which of these changes are healthy developments and which lead to serious diseases? This is what LifeTime, a new transnational and interdisciplinary initiative of leading European researchers, aims to discover. The consortium is jointly coordinated by the Max Delbrück Center in Berlin and the Institut Curie in Paris, with the Helmholtz Association and the CNRS. It has now cleared an important hurdle: LifeTime will be given one million euros and one year to develop a plan to embed its vision for a healthier future within the European research and innovation landscape.

How can we detect the first signs of disease as early as possible? Could closer investigation at the cellular level help to quickly prevent disease progression through appropriate treatment? The European Union is now investing a million euros over a one-year period to devise the plan for a fundamentally new approach to understanding the constant changes within cells and their relationships to one another, thus creating the foundation for the precision medicines of the future. These funds will go to the international LifeTime consortium, which is jointly coordinated by the Max Delbrück Center for Molecular Medicine (MDC) and the Institut Curie.

The two largest European research organizations – Germany’s Helmholtz Association and the National Centre for Scientific Research (CNRS) in France – are playing a major role in the project. More than 120 scientists at 53 institutions in 18 European countries are supporting the LifeTime consortium, as are more than 60 partners from industry. The European Union will concurrently fund the preparation of five other potential research initiatives. After the first year of funding, it will be up to the European Union to decide if any of them will be continued as a large-scale research initiative.

Precise therapeutic strategies

If a 58-year-old woman experiences a heart attack, there is currently only one option available to her. Physicians will use a cardiac catheter to look for obstructed or narrowed blood vessels and then treat her according to textbook protocols. The procedure might look different in the future: Physicians first take a tiny sample at the site of the heart attack. They then sequence the RNA which is expressed there by the DNA in individual cells, thereby identifying the cell aggregates that have become inflamed and that can either heal the aftereffects of the heart attack or cause additional damage.

What is crucial here is the development of innovative technologies that enable scientists to not only analyze cell populations, but also study individual cells in detail. Data gathered this way can be used by physicians to design precise therapeutic strategies.

This vision of precision medicine cannot be realized by only gathering human behavioral data from smartphones and wearable microcomputers – so-called wearables. Instead, it requires an understanding of how individual cells in our body change over time. That is because cells are not static components, but rather dynamic units that undergo constant transformation. Even when we are healthy, our cells develop and multiply, form tissues with numerous other cells, acquire new characteristics, or simply age all the time. Such change can be a normal development or lay the foundation for disease. Cells are especially prone to change over the course of the disease process.

Unlocking the future: single-cell biology, organoids, and AI

LifeTime’s research teams bring together cutting-edge technologies and by collaborating within the project and they can significantly push forward their development in Europe. For example, miniature organs grown in the petri dish – so-called organoids – and other innovative system such as new single-cell biology techniques – recently selected as Science’s breakthrough of 2018 – play a crucial role here. The organoids derived from patients’ stem cells enable the development of personalized disease models. Combined with the genome editing tool CRISPR, as well as state-of-the-art microscopy, and other models they will help scientists understand how cells stay healthy or progress towards disease and react to therapeutics.

The experiments – performed using high-throughput methods – generate huge amounts of data. Machine learning and artificial intelligence are therefore required for the analysis. The computational strategies identify patterns in the transformation of cells and can, for example, predict the onset of a disease or how a disease will progress. Together with mathematical models that enable the reconstruction of the cells’ past development, it is thus possible to infer how healthy cells become unhealthy cells. The scientists are also searching for central controls that can reverse or even completely prevent disease-causing changes.

The proposed groundbreaking initiative brings together not only researchers from the fields of biology, physics, computer science, mathematics, and medicine, but also experts from disciplines such as sociology, ethics, and economics. LifeTime researchers plan to include the public in their work by holding consultations early on to collect wider views and opinions on LifeTime and how it can meet the needs of European society. It is anticipated that the LifeTime initiative will significantly impact the pharma, biotech, and data processing industries, as well as other sectors, while also positively influencing Europe’s competitiveness.

More than 60 companies, major European research organizations such as the Helmholtz Association in Germany, the National Centre for Scientific Research (CNRS) in France, the Wellcome Trust in the United Kingdom, the Netherlands Organisation for Scientific Research (NWO), and the EU-LIFE Alliance, as well as several national science academies are already supporting LifeTime. “LifeTime is an outstanding project of European pioneers. This interdisciplinary and international cooperation has the potential to raise health research, and thus medical care to a new level. Therefore, we are very pleased that the EU is financing the LifeTime consortium. LifeTime is in the best sense: research for people,” says Otmar D. Wiestler, President of the Helmholtz Association.

A European vision

LifeTime will be receiving EU funding for one year to prepare a detailed plan for a ten-year research initiative. “This is a huge opportunity,” says Professor Nikolaus Rajewsky, who heads the MDC’s Berlin Institute for Medical Systems Biology (BIMSB), a hot spot for single-cell analyses. He is one of the two coordinators of the research consortium. “All of LifeTime’s members are among the best in their respective fields. They are doing visionary work. We are going to use this year to intensify our collaboration, share our vision and extend our network within Europe and beyond.” A launch conference will be held in Berlin from May 6 to 7, 2019, where the consortium’s members will introduce LifeTime and share information on how LifeTime plans to strengthen life sciences and healthcare in Europe.

The exact diseases the LifeTime initiative will focus on have yet to be selected. Refining the choice of disease will be a priority and will take into account a multitude of factors: “Europe’s citizens face a wide variety of medical conditions. During the first year, part of the plan is to determine which diseases are most amenable to our emerging technologies and models,” says Geneviève Almouzni, co-coordinator of the project, Research Director at the CNRS and director of the Research Center of the Institut Curie from 2013 to 2018. “We will do this with the aid of citizens, health professionals and policy makers. We foresee, that the diseases could include cancers but also heart diseases, nervous system disorders, or other diseases.”

International consortium

LifeTime is the shared vision of more than 120 leading scientists at over 50 renowned organizations across Europe, who selected 18 partners to submit the proposal.

21.12.2018 – Cell by cell for the breakthrough of the year

LifeTime consortium mentioned in Science

The editors of the scientific magazine “Science” have now chosen single cell analysis as the breakthrough of the year. According to “Science”, the single cell revolution has only just begun. LifeTime is on the right track; it will harness these technologies to understand human diseases.

30.10.2018 – LifeTime scientists and colleagues call for new standards

Studying the three-dimensional structure of DNA and its dynamics is revealing a lot of information about gene expression, expanding our knowledge of how cells, tissues and organs actually work in health and disease. Properly producing and managing this large amount of data is both challenging and necessary for the progress of this field. In a perspective paper published in Nature Genetics, top researchers call for unified standards and suggest guidelines in this emerging and promising research area.

Just as a map of the world is more than a list of places and street names, the genome is more than a string of letters. A complex choreography of proteins and nucleic acids interact differentially over time in the DNA, thus cells can selectively manage genetic information during development and cell differentiation or in response to physiological and environmental aspects.

Scientists worldwide are developing new technologies and making progress towards understanding the dynamics of three-dimensional organization of the nucleus. This new approach will allow researchers to map the differences between cell types, to explore how gene expression actually works in health or disease, and to discover how DNA functions are achieved even it is packed within the tiny nucleus.

“We know that genome folding and its dynamics modulates gene expression and new technologies allow us to build 3D models to study these changes, which is currently shaking up genome research and boosting our understanding of the cell nucleus complexity,” explains Marc A. Marti-Renom, ICREA research professor at the Centro Nacional de Análisis Genómico of the Centre for Genomic Regulation (CNAG-CRG) in Barcelona, Spain. “This is an absolutely promising field and we would like to call for standards since the rapid development of methods and the increasing complexity of data pose many challenges that must be addressed now,” he states.

In a perspective article published in the current issue of Nature Genetics, top leading scientists in the field of dynamics and structural genomics have called for standards in 3D genome and epigenetic data. They describe the main challenges in this field and provide guidelines to think about strategies for shared standardized validation of 4D nucleome data sets and models.

This paper comes out of their experience in the 4D Nucleome Initiative as part of the LifeTime initiative for a new FET-Flagship in Europe to understand how genomes function within cells, and how cells form tissues and dynamically remodel their activities when tissues progress towards disease.

18.09.2018 – 2nd stage proposal submitted!

The LifeTime initiative, which strives to build a new European FET-Flagship, has set sail for the next harbour: on Tuesday 18 September the proposal for a Coordination and Support Action (CSA) has been submitted to the European Commission. CSAs are preparatory actions, funded with €1 Mio for one year, with the aim to prepare the full Flagship application. The results are expected towards the end of 2018, with a CSA starting approximately half a year later.

LifeTime is the shared vision of more than 120 leading scientists at over 50 renowned organisations across Europe, who selected 18 partners to lead the preparatory work for the FET-Flagship.

LifeTime has gathered more then 60 partners from industry and received letters of support from major funding agencies, science academies and science and research ministries across Europe.

Many thanks to all the supporters, partners and contributors who helped the initiative to move one step closer to the realisation of the LifeTime vision.

22.03.2018 – LifeTime Press Release

LifeTime – a visionary proposal for an EU Flagship

Reliably predicting the onset and trajectory of a disease might seem like a distant dream. But a European consortium is aiming to achieve exactly this using a set of emerging technologies with the analysis of single cells at their core. Leading scientists have now submitted the proposal for a FET Flagship called LifeTime.

Following the completion of the Human Genome Project in 2001, scientists and the media described the genome as “the book of life”, holding the answers to the way genes are linked to disease. Yet, seventeen years later, we are still deciphering how cells interpret this book.

Since then, so-called Omics technologies have flourished, allowing researchers, for example, to observe and quantify thousands of gene products in a single tissue sample. Omics experiments used to require tens of thousands of cells. But in the last couple of years, novel single-cell methods have emerged which enable scientists to perform such global analyses in individual cells. The molecular make-up of tissues and organs can now be assessed at single-cell resolution.

Snapshots are not enough

Mapping and analyzing tissues at the single-cell level is highly informative and challenging by itself, but a diverse group of 60 scientists across Europe decided that merely taking snapshots is not enough. Cells are highly dynamic entities and may even change identities. To understand molecular forces behind different cell states in development, aging and disease, these scientists want to track the molecular make-up of human cells in time and space. To this end, they formed the LifeTime consortium with the goal of establishing an integrated toolbox containing several novel revolutionary methods.

Single-cell technologies will be applied to experimental model systems such as organoids, miniature organs grown in the petri dish from one or more cells. Combined with the genome editing tool CRISPR/Cas as well as state-of-the-art microscopy, these models will help to understand how cells stay healthy or progress towards disease and react to therapeutics. Importantly, LifeTime scientists will also develop computational strategies such as powerful machine-learning and artificial intelligence methods that help to understand molecular mechanisms and predict the future of a patient’s tissue or even means to steer the tissue towards health. This strategy is expected to improve early diagnoses and intervention, predict the course of a disease, identify new drug targets and select the most effective therapies for individual patients.

A group of pioneers

Future and Emerging Technologies Flagships (such as the ongoing Human Brain Project, the Graphene and the Quantum Technologies Flagship) are funded by the European Commission with one billion Euros for ten years. The competition for the next two Flagships has just started, and proposals have been submitted. LifeTime – jointly coordinated by the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) in Berlin and the Institut Curie in Paris – is one of them.

Currently the LifeTime consortium consists of over 60 leading single-cell biologists, computer scientists, mathematicians, clinicians, pathologists, imaging experts, and physicists from over 50 European institutions in 18 countries. They are pioneers in their disciplines, working towards a common vision of future medicine, and would like LifeTime to be an open endeavor that will attract new talents and integrate all scientists in Europe who can make a significant contribution. Theirunique collective network will transcend institutional boundaries and improve the overall infrastructure for the life sciences in Europe, with a focus on training for the next generation of scientists.

Steer life sciences and healthcare to the future

The LifeTime consortium will build on the achievements of the Human Cell Atlas (HCA), an international project launched about a year ago. The HCA aims to create a map of healthy tissues with single-cell technologies, thereby capturing the enormous diversity of cell types within those tissues. LifeTime proposes to go far beyond providing static tissue maps and to track, understand and predict how the molecular make-up of cells changes during human diseases and ultimately intervene.

It is a vision that can steer both life sciences and healthcare into the future and kick-start a single-cell innovation ecosystem in Europe. Many technologies at the center of LifeTime are key European research strengths that the Flagship could boost. These include single-cell technologies combined with advanced imaging, artificial intelligence and patient-matched organoids, or organ-on-a-chip disease models to study the progression of an illness and develop novel therapeutics.

Inspiration from Renaissance Europe

As an inspiration, LifeTime scientists name Renaissance Europe. Back then, new types of telescopes permitted Brahe, Galileo and Kepler to accurately map the precise positions of stars and planets. They were able to decode the patterns in these maps thanks to new types of mathematics developed by Leibniz and Newton, and thus discovered that celestial bodies moved in rule-governed and therefore predictable ways. Their efforts reshaped the society of their time.

Similarly, emerging technologies now allow scientists to observe cells (corresponding to planets in this analogy) and entire organs (corresponding to solar systems) with unprecedented precision. New mathematical and computational tools will be required to understand the movement and relationships of those cells. The resulting ability to explain cellular changes as they age or progress towards disease will fundamentally change our perception of how organisms function and will greatly advance medicine.

The LifeTime consortium

The more than 60 scientists and clinicians forming the LifeTime consortium are distributed over 18 European countries and 52 institutions. Both the Helmholtz Association of German Research Centres and the French National Center for Scientific Research CNRS – two of the biggest science organizations in Europe – have pledged their strong support. Furthermore, the consortium is endorsed by Science Academies such as the German National Academy of Sciences Leopoldina, the French Academy of Sciences, the Royal Society and the Royal Netherlands Academy of Sciences and Arts and the EU-life Alliance. Professor Nikolaus Rajewsky, Director of the Berlin Institute for Medical Systems Biology at the Max Delbrück Center for Molecular Medicine, and Professor Geneviève Almouzni, CNRS senior researcher and director of the research center at Institut Curie in Paris, are jointly coordinating the LifeTime proposal.

We provide a novel dissociation approach for #SingleCell RNA-seq. Cells are fixed from start, can be frozen multiple times, labelled and sorted. With this, we profile ~34K planarian cells using SPLiT-seq.
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